McInerney-Leo et al. (2013) studied a nonconsanguineous Australian family of British and Maori descent in which the healthy parents had 2 offspring with short-rib polydactyly syndrome, clinically classified as SRPS type III (see 263510). The first child presented ... McInerney-Leo et al. (2013) studied a nonconsanguineous Australian family of British and Maori descent in which the healthy parents had 2 offspring with short-rib polydactyly syndrome, clinically classified as SRPS type III (see 263510). The first child presented with short long bones on ultrasound at 6 weeks' gestation. Follow-up ultrasound at 31 weeks' showed polyhydramnios, severe shortening of long bones with bowed femurs, macrocephaly, short ribs, and ambiguous genitalia. Born at 32 weeks' gestation, the baby died at 2 hours of life. Autopsy confirmed the above findings and in addition revealed postaxial polydactyly of both hands, syndactyly of some fingers and toes, acetabular spurs, pancreatic fibrosis, mild dilation of renal tubules, and enlarged liver with ductal plate malformation. A second pregnancy was terminated at 17 weeks' gestation after ultrasound showed short ribs and short bowed limbs. Autopsy further revealed brachydactyly (not polydactyly), conical epiphyses, hypoplastic trabecular bone, depressed nasal bridge, ventricular septal defect (VSD), focal cystic changes in the kidneys, prominent bile ducts, and early evidence of pulmonary hypoplasia.
In the deceased proband from a nonconsanguineous Australian family of British and Maori descent segregating autosomal recessive short rib-polydactyly syndrome, McInerney-Leo et al. (2013) performed whole-exome sequencing and identified compound heterozygosity for a nonsense (Q631X; 615462.0001) and a ... In the deceased proband from a nonconsanguineous Australian family of British and Maori descent segregating autosomal recessive short rib-polydactyly syndrome, McInerney-Leo et al. (2013) performed whole-exome sequencing and identified compound heterozygosity for a nonsense (Q631X; 615462.0001) and a missense (T749M; 615462.0002) mutation in the WDR60 gene. An affected fetus in the family was also compound heterozygous for the mutations, whereas the unaffected parents were each heterozygous for 1 of the mutations. The authors reviewed exome sequencing data from 1,985 unrelated individuals but found no compound heterozygotes carrying WDR60 mutations. However, a review of exome sequencing data from 54 patients with skeletal ciliopathies revealed a 5-year-old Spanish boy, originally diagnosed with Jeune syndrome (see 208500), who was compound heterozygous for mutations in WDR60: the T749M missense mutation and a splice site mutation (615462.0003). In the Spanish boy, prenatal ultrasound had shown short femurs, and at birth he was noted to have narrow chest, preaxial polydactyly on the right hand, and a clinically insignificant VSD. At 1 year of age, he showed signs of failure to thrive, and at 5.25 years of age, his height and weight were below the fifth centile for age. X-rays showed mildly narrowed thorax, 'handlebar' clavicles, and acetabular spurs. He had no evidence of renal, hepatic, retinal, neurologic, or developmental problems. Haplotype analysis excluded a common founder for the shared missense mutation.